Every client project is a unique proposition, hence the requirement for a collaborative approach. MicroMatrices possesses an evolving array of applications. Many of these support Mode of Action understanding, which can be used to generate hypotheses and design bespoke investigatory studies, to help develop a Threshold Based Risk Assessment and Human Relevance argument.
The SpheroMatrices® array technology (patent pending) unlocks the biology contained within 3D spheroid model experiments by making simultaneous physical sections through all the spheroids in an experiment, retaining the 96 well plate format.
The spheroid array sections can be probed by multiplex immunofluorescence staining and/or in situ hybridisation and analysed by automated image analysis scripts for a wide variety of end points, an approach which overcomes the light scatter and quenching issues inherent in trying to image whole spheroids.
This approach de-risks drug development by identifying targets that would not be detected with currently available platforms so serves as a valuable supplement to current platforms. For more information, please visit www.spheromatrices.com.
MicroMatrices offer retrospective study analyses. We extract RNA from archival FFPE tissue blocks for use in integrated miRNA/mRNA array investigations and unbiased and focused pathways analysis. We can then further explore molecular pathology using immunohistochemistry (IHC), RNAscope in situ hybridisation (ISH) colocalisation, image analysis, etc. These combined approaches unlock the potential of historic samples and aids the design of bespoke prospective investigative studies whilst reducing the need for new animal experiments. An example of this approach can be found in Case Study 1.
LDT facilitates focused exploration of FFPE or frozen tissues from investigative studies. The combination of laser microdissection, microarray, and molecular pathology techniques results in a powerful approach to tissue analysis for exploring molecular markers and pathway perturbations. The technique yields sufficient mRNA to enable a tissue region-specific unbiased pathways analysis for the identification of several candidate genes, and gene expression pathways for hypothesis generation and testing.
An example of this approach can be found in Case Study 2.
MicroMatrices are experts in the use of RNAscope technology, capable of detecting and visualising a single RNA transcript within a cell with high sensitivity/specificity and little to no background, in combination with immunohistochemistry staining and colocalisation to offer clients a unique target visualisation capacity which can guide and/or corroborate mechanistic and mode of action studies. For an example of this application, please see Case Study 1.
Where intracellular drug targets/biomarkers or other molecules of interests can be visualised via immunostaining, the algorithms developed for use in WSIA allow for quantification and direct comparison of targets within different samples/tissues, solving tissue heterogeneity issues and facilitating inter study comparisons. Our WSIA flyer contains further information on the benefits of this methodology as well as a sample application.
Zebrafish (ZF) toxicity profiles are strikingly similar to those found in mammals. MicroMatrices employ this model system in combination with microarray and pathways analysis for the detection of potential biomarkers of developmental toxicity as well as the investigation of the mode of action of toxicants. Detection of Biomarkers for Developmental Toxicity in Zebrafish.
We can support in early discovery, development, and product life cycle maintenance. Should registration concerns arise as a consequence of regulatory tests with model species, MicroMatrices can assist. We will undertake mechanism-based risk assessment analyses to investigate hypotheses of toxicity and determine whether a case for non-human relevance can be demonstrated, potentially extending the commercial life of the product.
A demonstration of this approach can be seen in Case Study 1.
MicroMatrices possess a varied and adaptable toolbox of molecular profiling techniques for the discovery of novel biomarkers for toxicity and will custom design assays to address the unique requirements of our clients. Case Study 2 provides an example of the approaches which can be used in the identification of mechanistic biomarkers within target cells.
MicroMatrices’ array of technologies are well suited to exploring and demonstrating xenobiotic targets, using both in situ hybridisation (ISH) and immune staining (IHC). The unique sensitivity of RNAscope, in particular, enables highly specific localisation. An example of the application of this approach is contained in Case Study 3, where we demonstrate the mapping of GABA isoforms.
MicroMatrices will assist in the preparation and review of manuscripts for publication, study reports, SOPs, and other technical documents; please enquire.
on an interactive, step by step basis. Collaborations can begin with pilot projects which can then be scaled up to larger research programs, according to your requirements.